Lithium Hydroxide → 2-((S)-5-(3-(5-(4,5-dimethylthiazol-2-yl)pyridin-2-yloxy)propoxy)-2,3-dihydro-1H-inden-1-yl)acetic acid

HRID 2235919Notes

Reaction equation

HRID 2235919 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][O:18][C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[C@H:24]([CH2:28][C:29]([O:31]CC)=[O:30])[CH2:23][CH2:22]4)=[N:12][CH:13]=2)[S:5][C:6]=1[CH3:7].[Li+].[OH-]>C1COCC1.CO.O>[CH3:1][C:2]1[N:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][O:18][C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[C@H:24]([CH2:28][C:29]([OH:31])=[O:30])[CH2:23][CH2:22]4)=[N:12][CH:13]=2)[S:5][C:6]=1[CH3:7]

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 59300420ethyl [(1S)-5-(3-{[5-(4,5-dimethyl-1,3-thiazol-2-yl)-2-pyridinyl]oxy}propoxy)-2,3-dihydro-1H-inden-1-yl]acetate

Product 1

HCID 99805712-((S)-5-(3-(5-(4,5-dimethylthiazol-2-yl)pyridin-2-yloxy)propoxy)-2,3-dihydro-1H-inden-1-yl)acetic acidYield 89.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl [(1S)-5-(3-{[5-(4,5-dimethyl-1,3-thiazol-2-yl)-2-pyridinyl]oxy}propoxy)-2,3-dihydro-1H-inden-1-yl]acetate (Example 260) (80 mg, 0.17 mmol) in THF (2 mL), methanol (2 mL) and water (1 mL) was added LiOH (40 mg, 1.74 mmol). The reaction mixture was stirred at rt for 18 h, and then concentrated under reduced pressure. The residue was taken up in water and acidified with a 5% aqueous solution of H3PO4, and extracted with EtOAc. The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure to give the product (67 mg, 89%). 1H NMR (400 MHz, CD2Cl2) δ 8.57 (d, 1H), 8.06 (dd, 1H), 7.09 (d, 1H), 6.85 (d, 1H), 6.80 (d, 1H), 6.71 (dd, 1H), 4.53 (t, 2H), 4.15 (t, 2H), 3.49 (qt, 1H), 2.92-2.75 (m, 2H), 2.71 (dd, 1H), 2.45-2.28 (m, 8H), 2.32-2.22 (m, 2H), 1.82-1.70 (m, 1H); LC-MS: RT=3.41 min, (M+H)+ 439.0.

Workup

  1. concentrationconcentrated under reduced pressure
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f991d80486964041834ba79b66596c33
Source dataset
uspto-grants-2010_05
Patent number
US07714004B2

Reaction notes

Loading…